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Validation of in vivo magnetic resonance imaging blood-brain barrier permeability measurements by comparison with gold standard histology.

ABSTRACT: We sought to validate the blood-brain barrier permeability measurements extracted from perfusion-weighted MRI through a relatively simple and frequently applied model, the Patlak model, by comparison with gold standard histology in a rat model of ischemic stroke.Eleven spontaneously hypertensive rats and 11 Wistar rats with unilateral 2-hour filament occlusion of the right middle cerebral artery underwent imaging during occlusion at 4 hours and 24 hours after reperfusion. Blood-brain barrier permeability was imaged by gradient echo imaging after the first pass of the contrast agent bolus and quantified by a Patlak analysis. Blood-brain barrier permeability was shown on histology by the extravasation of Evans blue on fluorescence microscopy sections matching location and orientation of MR images. Cresyl-violet staining was used to detect and characterize hemorrhage. Landmark-based elastic image registration allowed a region-by-region comparison of permeability imaging at 24 hours with Evans blue extravasation and hemorrhage as detected on histological slides obtained immediately after the 24-hour image set.Permeability values in the nonischemic tissue (marginal mean ± SE: 0.15 ± 0.019 mL/min 100 g) were significantly lower compared to all permeability values in regions of Evans blue extravasation or hemorrhage. Permeability values in regions of weak Evans blue extravasation (0.23 ± 0.016 mL/min 100 g) were significantly lower compared to permeability values of in regions of strong Evans blue extravasation (0.29 ± 0.020 mL/min 100 g) and macroscopic hemorrhage (0.35 ± 0.049 mL/min 100 g). Permeability values in regions of microscopic hemorrhage (0.26 ± 0.024 mL/min 100 g) only differed significantly from values in regions of nonischemic tissue (0.15 ± 0.019 mL/min 100 g).Areas of increased permeability measured in vivo by imaging coincide with blood-brain barrier disruption and hemorrhage observed on gold standard histology.

SUBMITTER: Hoffmann A

PROVIDER: S-EPMC3921072 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Validation of in vivo magnetic resonance imaging blood-brain barrier permeability measurements by comparison with gold standard histology.

Hoffmann Angelika A Hoffmann Angelika A Bredno Jörg J Wendland Michael F MF Derugin Nikita N Hom Jason J Schuster Tibor T Su Hua H Ohara Peter T PT Young William L WL Wintermark Max M

Stroke 20110602 7

<h4>Background and purpose</h4>We sought to validate the blood-brain barrier permeability measurements extracted from perfusion-weighted MRI through a relatively simple and frequently applied model, the Patlak model, by comparison with gold standard histology in a rat model of ischemic stroke.<h4>Methods</h4>Eleven spontaneously hypertensive rats and 11 Wistar rats with unilateral 2-hour filament occlusion of the right middle cerebral artery underwent imaging during occlusion at 4 hours and 24 h ...[more]

PMID: 21636816

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Project description:Key pointsThe blood-brain barrier (BBB) is an important and dynamic structure which contributes to homeostasis in the central nervous system. BBB permeability changes occur in health and disease but measurement of BBB permeability in humans is not straightforward. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to model the movement of gadolinium contrast into the brain, expressed as the influx constant Ki . Here evidence is provided that Ki as measured by DCE-MRI behaves as expected for a marker of overall BBB leakage. These results support the use of DCE-MRI for in vivo studies of human BBB permeability in health and disease.AbstractBlood-brain barrier (BBB) leakage can be measured using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as the influx constant Ki . To validate this method we compared measured Ki with biological expectations, namely (1) higher Ki in healthy individual grey matter (GM) versus white matter (WM), (2) GM/WM cerebral blood volume (CBV) ratio close to the histologically established GM/WM vascular density ratio, (3) higher Ki in visibly enhancing multiple sclerosis (MS) lesions versus MS normal appearing white matter (NAWM), and (4) higher Ki in MS NAWM versus healthy individual NAWM. We recruited 13 healthy individuals and 12 patients with MS and performed whole-brain 3D DCE-MRI at 3 T. Ki and CBV were calculated using Patlak modelling for manual regions of interest (ROI) and segmented tissue masks. Ki was higher in control GM versus WM (P = 0.001). CBV was higher in GM versus WM (P = 0.005, mean ratio 1.9). Ki was higher in visibly enhancing MS lesions versus MS NAWM (P = 0.002), and in MS NAWM versus controls (P = 0.014). Bland-Altman analysis showed no significant difference between ROI and segmentation methods (P = 0.638) and an intra-class correlation coefficient showed moderate single measure consistency (0.610). Ki behaves as expected for a compound marker of permeability and surface area. The GM/WM CBV ratio measured by this technique is in agreement with the literature. This adds evidence to the validity of Ki measured by DCE-MRI as a marker of overall BBB leakage.

Project description:ObjectiveThe objective was to quantitatively evaluate the validity of ultrasonographic (US) muscle measurements as compared to the gold standard of computed tomography (CT) in the canine.DesignThis was a prospective study.PopulationTwenty-five, client-owned dogs scheduled for CT as part of a diagnostic work-up for the management of their primary disease process were included.Materials and methodsSpecific appendicular (cubital flexors and extensors, coxofemoral flexors and extensors) and axial (temporalis, supraspinatus, infraspinatus, lumbar epaxials) muscle groups were selected for quantitative measure based on CT planning and patient position. Prior to CT scan, the skin over the muscle sites was shaved and marked with a permanent marker. Patient body position was determined based on the patient's CT plan; positioning was consistent between CT and US imaging. To ensure identical imaging position for both CT and US measurements, radio-opaque fiducial markers were placed directly over the skin marks once the dog was positioned. Quantitative measurements (cm) for both lean muscle mass (LMM) and subcutaneous adipose (SQA) were recorded. Statistical comparisons between CT and US values were done separately for each site and type.ResultsMuscle groups and associated SQA measured by US and CT were not statistically different based on an adjusted p-value using Bonferroni's correction (p < 0.0031). In addition, all LMM and SQA sites had good reliability and agreement (Cronbach's ? = 0.8 - 1.0) between the two metrics, excluding the coxofemoral extensor muscle group (Cronbach's ? = 0.73232). Linear regression analysis of muscle measures indicated close agreement (slope range 0.93-1.09) and minimal bias of variation (intercept range 0.05-0.11) between CT versus US modalities, with the exception of the coxofemoral extensor muscle. Similarly, SQA CT and US measures indicated close agreement with the slope range of 0.88-1.02 and minimal bias of variation with an intercept range of 0.021-0.098, excluding the cubital flexor and extensor groups. Additionally, the R2 values for these remaining LMM and SQA sites are reported as >0.897 for LLM and >0.8289 for SQA.ConclusionsUltrasound imaging of selected appendicular and axial muscle groups in dogs can provide comparable assessment of muscle thickness to the current gold standard, CT. In consideration of both statistical reliability to CT and cage-side accessibility, the temporalis, supraspinatus, infraspinatus, and lumbar epaxial LMM sites are considered the most useful targets for US LMM assessment in the canine. Our findings support the potential utility of US as a clinical tool in veterinary medicine to assess LMM status in patients. Additional studies are indicated to develop standardized protocols of its use in a cage-side setting and to elucidate the benefit of this modality, in conjunction with nutritional interventions, to manage body LLM stores in compromised patients.

Project description:BackgroundTechnical advances in perfusion cardiovascular magnetic resonance (CMR), particularly accelerated data acquisition methods, allow myocardial perfusion imaging with unprecedented spatial resolution. However, it is not clear how implementation of these recent advances affects perfusion image quality, signal and contrast to noise ratios (SNR & CNR) and the occurrence of important artefacts in routine clinical imaging. The objective of this study was therefore to compare a standard and an advanced, high-resolution perfusion sequence.MethodsA standard ultrafast gradient echo perfusion sequence (st-GrE) was compared with an advanced kt-accelerated steady state free precession sequence (ktBLAST-SSFP) at 1.5 T in healthy volunteers (n = 16) and in patients (n = 32) with known or suspected coronary artery disease. Volunteers were imaged with both sequences at rest and patients underwent stress and rest imaging with either st-GrE or ktBLAST-SSFP prior to X-ray coronary angiography.A blinded expert scored image quality and respiratory artefact severity and also classified patients for the presence of CAD. The extent, transmurality and duration of dark rim artefacts (DRA) as well as signal to noise (SNR) and contrast to noise (CNR) were quantified.ResultsIn normal hearts ktBLAST-SSFP imaging resulted in significantly improved image quality (p = 0.003), SNR (21.0 ± 6.7 vs. 18.8 ± 6.6; p = 0.009), CNR (15.4 ± 6.1 vs. 14.0 ± 6.0; p = 0.034) and a reduced extent (p = <0.0001) and transmurality (p = 0.0001) of DRA. In patients ktBLAST-SSFP imaging resulted in significantly improved image quality (p = 0.012), and a reduced extent (p = <0.0001), duration (p = 0.004) and transmurality (p = <0.0001) of DRA. Sensitivity and specificity for the detection of CAD against X-ray angiography was comparable with both sequences. There was a non-significant trend towards increased respiratory artefacts with ktBLAST-SSFP in both patients and volunteers.ConclusionsAdvanced high resolution perfusion CMR using a k-t-accelerated SSFP technique results in significantly improved image quality, SNR and CNR and a reduction in the extent and transmurality of DRA compared to a standard sequence. These findings support the use of advanced perfusion sequences for clinical perfusion imaging however further studies exploring whether this results in improved diagnostic accuracy are required.

Project description:BackgroundRenal fibrosis is a key driver of progression in chronic kidney disease (CKD). Recent advances in diagnostic imaging techniques have shown promising results for the noninvasive assessment of renal fibrosis. However, the specificity and accuracy of these techniques are controversial because they indirectly assess renal fibrosis. This limits fibrosis assessment by imaging in CKD for clinical practice. To validate magnetic resonance imaging (MRI) assessment for fibrosis, we derived representative models by mapping histology-proven renal fibrosis and imaging in CKD.MethodsNinety-seven adult Chinese CKD participants with histology were studied. The kidney cortex interstitial extracellular matrix volume was calculated by the Aperio ScanScope system using Masson's trichrome slices. The kidney cortex microcirculation was quantitatively assessed by peritubular capillary density using CD34 staining. The imaging techniques included intravoxel incoherent motion diffusion-weighted imaging and magnetic resonance elastography (MRE) imaging. Relevant analyses were performed to evaluate the correlations between MRI parameters and histology variables. Multiple linear regression models were used to describe the relationships between a response variable and other variables. The best-fit lines, which minimize the sum of squared residuals of the multiple linear regression models, were generated.ResultsMRE values were negatively associated with the interstitial extracellular matrix volume (Rho = -0.397, p < 0.001). The best mapping model of extracellular matrix volume with the MRE value and estimated glomerular filtration rate (eGFR) we obtained was as follows: Interstitial extracellular matrix volume = 218.504 - 14.651 × In(MRE) - 18.499 × In(eGFR). DWI-fraction values were positively associated with peritubular capillary density (Rho = 0.472, p < 0.001). The best mapping model of peritubular capillary density with DWI-fraction value and eGFR was as follows: Peritubular capillaries density = 17.914 + 9.403 × (DWI - fraction) + 0.112 × (eGFR).ConclusionsThe study provides histological evidence to support that MRI can effectively evaluate fibrosis in the kidney. These findings picture the graphs of the mapping model from imaging and eGFR into fibrosis, which has significant value for clinical implementation.

Project description:PurposeCurrent cardiovascular magnetic resonance (CMR) examinations require expert planning, multiple breath holds, and 2D imaging. To address this, we sought to develop and validate a comprehensive free-breathing 3D cine function and flow CMR examination using a steady-state free precession (SSFP) sequence to depict anatomy fused with a spatially registered phase contrast (PC) sequence for blood flow analysis.MethodsIn a prospective study, 25 patients underwent a CMR examination which included a 3D cine SSFP sequence and a 3D cine PC (also known as 4D flow) sequence acquired during free-breathing and after the administration of a gadolinium-based contrast agent. Both 3D sequences covered the heart and mediastinum, and used retrospective vectorcardiogram gating (20 phases/beat interpolated to 30 phases/beat) and prospective respiratory motion compensation confining data acquisition to end-expiration. Cardiovascular measurements derived from the 3D cine SSFP and PC images were then compared with those from standard 2D imaging.ResultsAll 3D cine SSFP and PC acquisitions were completed successfully. The mean time for the 3D cine sequences including prescription was shorter than that for the corresponding 2D sequences (21 min vs. 36 min, P-value <0.001). Left and right ventricular end-diastolic volumes and stroke volumes by 3D cine SSFP were slightly smaller than those from 2D cine SSFP (all biases ≤5%). The blood flow measurements from the 3D and 2D sequences had close agreement in the ascending aorta (bias -2.6%) but main pulmonary artery flow was lower with the 3D cine sequence (bias -11.2%).ConclusionCompared to the conventional 2D cine approach, a comprehensive 3D cine function and flow examination was faster and yielded slightly lower left and right end-diastolic volumes, stroke volumes, and main pulmonary artery blood flow. This free-breathing 3D cine approach allows flexible post-examination data analysis and has the potential to make examinations more comfortable for patients and easier to perform for the operator.

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Validation of in vivo magnetic resonance imaging blood-brain barrier permeability measurements by comparison with gold standard histology.

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Validation of in vivo magnetic resonance imaging blood-brain barrier permeability measurements by comparison with gold standard histology.

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